Complications of Diabetes Mellitus

1. Complications of Diabetes Mellitus Dr Rodney Itaki Lecturer Anatomical Pathology Discipline University of Papua New Guinea School of Medicine & Health Sciences Division of Pathology

2. Clinical approach to Complications of DM Acute Complications • Ketoacidosis (Type I DM) • Hyperglycemic hyperosmolar non-ketotic syndrome (Type II DM) • Hypoglycaemia Chronic Complications • Macrovascular - hypertension • Microvascular – neuropapthies, nephropathies & retinopahty

3. Pathological Approach to Complications of DM • Microangiopathy – small vessel disease • Retinopathy • Nephropathy • Neuropathy • Underlying cause is hyperglycemia

4. Pathogenesis • Nonenzymatic Glycosylation • Formation of irreversible glycosylation products with protein (e.g collagen) in blood vessels and interstitial tissues. • Rather than dissociating, undergo series of slow series of chemical rearrangement that is irreversible forming Advanced Glycosylation End Products (AGE). • AGE resistant to enzymatic proteolysis

5. Non-enzymatic Glycosylation of Proteins Ref: Robins Pathological Basis of Diseases, 6th Ed.

6. Biological Properties of AGE Ref: Robins Pathological Basis of Diseases, 6th Ed.

7. Disturbance in Polyol Pathway • Occurs in nerves, lens, kidneys & blood vessels. Do not need insulin for glucose intake. • Osmotic cell injury • Impairs ion pumps - Schwann cells (peripheral & autonomic neurophathy), pericytes in retinal capillaries. (retinal microaneurysm) Ref: Robins Pathological Basis of Diseases, 6th Ed.

8. Morphology of Diabetes Complications • Pancreas: Most changes & more distinctive in Type I than Type II DM. • Reduction in number and size of islets • Leukocyte infiltration of islets (T lymphocytes mostly). • Eosinophil infiltrates • Amyloid replacement of islets in Type II. Islets obliterated in advanced Type II DM. • Vascular system: atherosclerosis of all vessels. Hyaline thickening of the wall of arterioles causing narrowing of lumen. • Diabetic microangiopathy: Diffuse thickening of BM of capillaries (skin, skeletal muscle, retina, renal glomeruli, renal medulla, renal tubules, Bowman’s capsule, peripheral nerves, and placenta). Hyaline material forming concentric layers – type IV collagen. Despite thickened BM, capillaries more leaky than normal to plasma proteins.

9. Morphology of Diabetes Complications • Diabetic nephropathy: glomerular lesions, renal vascular lesions (arteriosclerosis) & pyelonephritis, including necrotizing papillitis. • Glomerular lesions – capillary BM thickening, diffuse glomerularsclerosis, nodular glomerularsclerosis. • Renal vascular lesions – part of systemic involvement of blood vessels. Both afferent and efferent arterioles. • Pyelonephritis – due to acute or chronic inflammation. Begins in the interstitial tissue and spread to affect tubules. • Papillary necrosis more common in diabetics.

10. Morphological Complications of Diabetes • Diabetic Ocular complications: take the form of retinopathy, cataract formation and glaucoma. • Retinopathy – backgound (nonproliferative) & proliferative rentinopathy • Background retinopathy • BM thickening, • pericytedegeneration. Loss results in microaneurysms • capillary microaneurysms (hemorrhages) • Microvascular obstructions and non-perfusion of capillaries in posterior fundus that lack pericytes and endothelium. Cause hypoxia(cotton-wool spots). • Arteriolar hyalinization causing BM thickening. • Gradual increase in retinal vein caliber as response to ischaemia. Form venous loops and beading in veins.

11. Morpholigical Complications of Diabetes • Proliferative retinopathy – characterised by neovascularisation and fibroplasia. • Neovascularisation occurs in response to hypoxia of retina. • ischemic retinal cells produce VEGF (vascular endothelial growth factor) inducing angiogenesis from larger veins and arterial vessels. • new vessels incompletely formed & poorly supported and move with eye movements resulting in haemorrhages. • Fibroplasia results later & contribute to retinal detachment • Diabetic Neuropathy: central and peripheral nervous system. Pattern is of peripheral, symmetric neuropathy of lower limbs affecting both motor and sensory function.

12. Morphological complications of diabetes • Peripheral neuropathy – axonal neuropathy. Some segmental demyelination. • Endoneurial arterioles show hyalinization, BM thickening. • Neuropathies catergorised as: distal symmetric sensory (or sensorimoto) neuropathy, autonomic neuropathy & focal (or multifocal) asymmetric neuropathy. • Symmetric neuropathy affecting distal sensory and motor nerves common neuropathy. Autonomic neuropathy also common.

13. Clinical Presentation • Type I – younger (20 and below age at presentation. • Triad of P – polyuria, polyphagia and polydypsia. • Ketoacidosis – nausea, vomiting, respiratory symptoms • Ketoacidotic coma • Hypoglycaemic coma

14. Clinical Presentation • Type II – older age group. 30+. Usually obese. • Triad of Ps. • Routine medical check – common way to diagnose. Asymptometic. Unaware. • Hyperosmolar nonketotic coma. • Infection and septicaemia • Other complications – AMI, foot ulcer, cellulitis etc

15. Laboratory Diagnosis • Elevated blood glucose: non-fasting fasting >11.1 mmol/L; Fasting of >7.1 mmol/L. • Oral glucose tolerance test. • HBA1C – monitoring of control of blood glucose level.

16. Prognosis • Most patients die from • AMI • Chronic renal failure • CVA • Infections.

17. End Main Reference: Robins Pathological Basis of Diseases, 6th Ed. Chapter on The Pancreas. Download PPT notes on: www.pathologyatsmhs.wordpress.com